1. Field of the Invention
The present invention relates to drugs for inhibiting lentiviral activity and, more particularly, to a method for suppressing replication of the human immunodeficiency virus (HIV) by inhibitory mechanisms of a class of a crude extract of guaiacum officinale L. (Zygophyllaceae).
2. Description of the Background
There is great growth in the overlapping fields of biology, technology, and medicine, including remarkable advances in cellular biology that have given a new understanding of the molecular basis for some diseases. Nevertheless, there is currently no cure for HIV/AIDS. A number of natural products, mainly from plants, have been shown to possess anti HIV activity [Cragg G, Newman D. Plants as a source of anti-cancer and anti-HIV agents, Annals of Applied Biology, 143:127-33 (2003)]. This has resulted in the screening of thousands of plant extracts in search of effective drugs against HIV [Yang S S, Cragg G M, Newman D J, Bader J P, Natural product-based Anti-HIV Drug Discovery and Development Facilitated by the NCI Developmental Therapeutics Program, Journal of Natural Products, 64:265-77 (2001)]. The michellamine series of alkaloids and derivatives of betulinic acid are amongst some of the molecules isolated from plants with anti HIV activity [Boyd M R, Hallock Y F, Cardellina J H et al., Anti-HIV Michellamines From Ancistrocladus Korupensis. Journal of Medicinal Chemistry, 37:1740-5 (1994); Fujioka T, Kashiwada Y, Kilkuskie R E, et al., Anti-AIDS Agents, Betulinic Acid And Platanic Acid As Anti-HIV Principles From Syzigium Claviflorum And The Anti-HIV Activity Of Structurally Related Triterpenoids, Journal of Natural Products, 57:243-7 (1994)].
The Jamaican national flower, guaiacum officinale L., belongs to the Zygophyllaceae family and is commonly known as Lignum vitae. The plant is known to have a number of medicinal uses in folk medicine. For example, mixtures containing barks from guaiacum officinale L. and Maubi have been used in traditional Virgin Islands bush medicine to relieve fish poisoning [Singer G., Lignum Vitae, Guaiacum officinale at http://wwwstjohnbeachguidecom/Lignum%20Vitaehtm]. The flowers and leaves have been used to make a tea with energy restorative properties and as abortificient [Halberstein R., Traditional Botanical Remedies on a Small Caribbean Island: Middle (Grand) Caicos, West Indies. The Journal of Alternative And Complementary Medicine, 3:227-39, 7 (1997), Halberstein R A., Medicinal Plants: Historical And Cross-Cultural Usage Patterns, Annals of Epidemiology, 15:686-99 (2005)].
Elsewhere, there is anecdotal evidence that certain resins and extracts of guaiacum officinale L. have anti-inflammatory properties with activity against arthritis, gout and sciatica condition, and the resins of the plant are used in traditional medicines in Pakistan to cure angina, tonsillitis, rheumatoid arthritis, mucous membrane diseases and abnormalities of metabolic processes.
Guaiacum Officinale L. is known to be a rich source of saponins. Saponins are credited for several biological activities including membrane-permeabilising, immunostimulation and hypocholesterolaemic properties. Several mono and bidesmosidic saponins having akebonic acid and oleanolic acid as genins have previously been isolated and reported from this plant [Ahmad V U, Perveen S, Bano S., Saponins from the Leaves of Guaiacum officinale, Phytochemistry, 29:3287-90 (1990); Ahmad V U, Saba N, Khan K M., Triterpenoid Saponin From The Bark Of Guaiacum Officinale L., Natural Product Research, 18:111-6 (2004)]. Two guaiacum saponins, Guaiacin A and B, have been isolated from the leaves of Guaiacum officinale L. [Ahmad V U, Perveen S, Bano S., Guaiacin A and B from the Leaves of Guaiacum officinale, Planta Medica, 55:307-8 (1989)]. More recently, a new triterpenoidal saponin, guaianin N was isolated from the butanolic extract of the flowers of Guaiacum officinale L. [Saba N. Guaianin N, A New Saponin From Flowers Of Guaiacum Officinale, Pakistan Journal of Scientific and Industrial Research, 36:54-56 (1993)]. The Guaianin N showed antibacterial activity against Pseudomonas pseudomaliae as well as brine shrimp toxicity.
The present inventors have extracted a class of disaccharide arabinogalactan isolates from the indigenous plant and have applied them therapeutically to selectively inhibit HIV-1 in primary peripheral blood mononuclear cells (PBMCs) infected with the reference HIV-1 BaL strain, without substantial cytotoxicity activity to the PBMCs. Arabinogalactan is a biopolymer consisting of arabinose and galactose monosaccharides. The extract holds promise as a chemopreventive agent.